Mouse monoclonal antibodies reactive with gag or env proteins of Friend murine leukemia virus (F-MuLV) or recombinant MCF viruses related to F-MuLV were derived and characterized for viral protein specifically and reactivity with a large panel of MuLV's. Analysis of 10 strains of F-MuLV distinguished seven different antigenic phenotypes, all of which retained reactivity for three anti-gp70 antibodies uniquely specific for Friend and Rauscher MuLV's. Four antibodies with a unique reactivity for recombinant MCF viruses were also found. Most known MCF viruses react with at least one or two of these MCF-specific antibodies. F-MuLV inoculation of newborn mice was previously shown to induce leukemias in certain mouse strains. We have found that the predominant cell type in leukemia organs differed markedly in various mouse strains. Using a monoclonal anti-MCF virus antibody test as well as conventional MCF virus isolation, we observed a good correlation between appearance of MCF virus and presence of erythroid, myeloid or lymphoid leukemia in IRW mice. In contrast, in C57BL/10 mice only lymphoid and myeloid leukemias were observed and infections MCF viruses were never isolated. In (C57BL/10 X IRW)F1 mice, erythroid, myeloid, lymphoid and mixed leukemias were seen, but MCF viruses were isolated from only 25% of the mice. These results indicated that generation or expression of MCF viruses may not be necessary forleukemogenesis in some mouse strains or hemopoietic lineages.